Increased vulnerability of the blood-brain barrier to acute hypertension following depletion of brain noradrenaline.
Noradrenergic nerve terminals emanating from the pontine nucleus locus coeruleus (LC) have been suggested to take part in the regulation of intracerebral microvascular tone and, hence, blood flow. Since the extent of the blood-brain barrier opening caused by an acute hypertensive reaction previously has been shown to be highly dependent on the pre-existing cerebrovascular tone, we have explored whether selective depletion of brain noradrenaline (NA) would modify the albumin leakage caused by a hypertensive insult in the rat. Brain NA was largely and relatively selectively depleted, particularly in area innervated by the LC, by pretreatment with an injection of 6-hydroxydopamine (6-OHDA, 200 microgram) into the right lateral ventricle 7 days before the induction of an acute hypertensive reaction by intravenously administered angiotensin or adrenaline in conscious, unrestrained rats with indwelling catheters in the aorta and a jugular vein. 6-OHDA pretreatment significantly increased the leakage of 125 I-labelled albumin into the cortex after angiotensin-induced hypertension. A slight non-significant enhancement of protein in extravasation was observed after adrenaline administration. The latter substance caused, however, by itself a larger protein leakage probably related to betareceptor mediated vasodilatation. Whereas the increased permeability induced by adrenaline normally is reduced during the night, the albumin leakage was significantly increased in cortical regions in 6-OHDA treated rats in nocturnal experiments. The enhance protein leakage was not seen in rats treated with desmethylimipramine to prevent the uptake of 6-OHDA into the NA neurons.
D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D006892:Hydroxydopamines / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000032:analysis*; D016627:Oxidopamine; D051381:Rats; D012701:Serotonin / Q000032:analysis
D006892:Hydroxydopamines; D012701:Serotonin; D016627:Oxidopamine; D009638:Norepinephrine